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Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen

Item Type:Article
Title:Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen
Creators Name:Campos, L.A., Iliescu, R., Fontes, M.A.P., Schlegel, W.P., Bader, M. and Baltatu, O.C.
Abstract:We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta-adrenoceptor (beta-AR) agonist (isoproterenol, ISO). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, ISO induced a significantly greater increase LV pressure (dLVP) and maximal contraction ((+dP/dt)max), in the TGR than in the Sprague-Dawley (SD) rats. Left ventricular (LV) hypertrophy induced by ISO treatment was significantly higher in TGR than in SD rats (g LV weight/100 g body weight: 0.28 +/- 0.004 vs 0.24 +/- 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta-AR and upregulation of LV beta-AR kinase 1 (betaARK1) mRNA levels in comparison to SD rats. The decrease in the heart rate (HR) induced by the beta-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared to SD (-9.9 +/- 1.7 % vs. -18.1 +/- 1.5 %), while the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that transgenic rats with low brain angiotensinogen are more sensitive to beta-AR agonist induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.
Keywords:Renin-angiotensin system, Autonomic nervous system, Cardiac hypertrophy, Animals, Rats
Source:American Journal of Physiology Heart and Circulatory Physiology
Publisher:American Physiological Society
Page Range:H2371-H2376
Date:1 November 2006
Official Publication:https://doi.org/10.1152/ajpheart.01145.2005
PubMed:View item in PubMed

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